Varney, A.M. orcid.org/0000-0002-5943-161X, Smitten, K.L., Southam, H.M. et al. (4 more authors) (2024) In vitro and in vivo studies on a mononuclear ruthenium complex reveals it is a highly effective, fast-acting, broad-spectrum antimicrobial in physiologically relevant conditions. ACS Infectious Diseases, 10 (9). pp. 3346-3357. ISSN 2373-8227
Abstract
The crystal structure of a previously reported antimicrobial RuII complex that targets bacterial DNA is presented. Studies utilizing clinical isolates of Gram-negative bacteria that cause catheter-associated urinary tract infection, (CA)UTI, in media that model urine and plasma reveal that good antimicrobial activity is maintained in all conditions tested. Experiments with a series of Staphylococcus aureus clinical isolates show that, unlike the majority of previously reported RuII-based antimicrobial leads, the compound retains its potent activity even in MRSA strains. Furthermore, experiments using bacteria in early exponential growth and at different pHs reveal that the compound also retains its activity across a range of conditions that are relevant to those encountered in clinical settings. Combinatorial studies involving cotreatment with conventional antibiotics or a previously reported analogous dinuclear RuII complex showed no antagonistic effects. In fact, although all combinations show distinct additive antibacterial activity, in one case, this effect approaches synergy. It was found that the Galleria Mellonella model organism infected with a multidrug resistant strain of the ESKAPE pathogen Acinetobacter baumannii could be successfully treated and totally cleared within 48 h after a single dose of the lead complex with no detectable deleterious effect to the host.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2024 The Authors. This publication is licensed under CC-BY 4.0 - https://creativecommons.org/licenses/by/4.0/ |
Keywords: | AMR; ESKAPE; Galleria; combinatorial therapy; ruthenium; Animals; Anti-Bacterial Agents; Microbial Sensitivity Tests; Ruthenium; Moths; Staphylococcus aureus; Humans; Urinary Tract Infections; Coordination Complexes; Staphylococcal Infections |
Dates: |
|
Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Mathematical and Physical Sciences |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 23 Sep 2024 14:44 |
Last Modified: | 23 Sep 2024 14:44 |
Status: | Published |
Publisher: | American Chemical Society (ACS) |
Refereed: | Yes |
Identification Number: | 10.1021/acsinfecdis.4c00447 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:217515 |